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A prospective survey of laboratory records was carried out to identify the extent of drug induced hepatotoxicity in a hospital population. Eleven of 1000 (1.1%) abnormal liver function tests were due to drug induced hepatotoxicity. Anti-tubercular drugs, viz isoniazid, rifampicin and pyrazinamide were responsible for all cases of serious hepatotoxicity.
A 72-year-old female patient was diagnosed as having a tumor in her bladder at the department of obstetrics and gynecology. Transurethral resection of bladder tumor was performed in November, 2002. Pathology showed transitional cell carcinoma (TCC), G2>G3, pT1. Chemotherapy consisting of methotrexate, adriamycin and cisplatin and bladder instillation of Bacillus Calmette-Guerin (BCG) was performed. Re-biopsy revealed transitional cell carcinoma, G2, carcinoma in situ of the bladder and she received radical cystectomy with ureterocutaneostomy in June, 2003. After the cystectomy, the left ureter showed signs of cancer so BCG was administered through the left ureterocutaneostomy. During the second instillation, she had a high temperature and also exhibited signs of chills with frequent shivering followed by dyspnea, severe hypotension and tachycardia. We started the patient on dopamine and norepinephrine drips to maintain blood pressure and then started isoniazide and meropenem for presumed septic shock. The next day, the patient continued to be febrile and her condition deteriorated. After she was given endotoxin absorption therapy, she regained normal blood pressure and her heart rate, but was still febrile. After 13 days, rifampicin, ethambutol, and pyrazinamide were administered and after 18 days predonisolone was begun. From that point the patient's general condition gradually improved.
A 50-year-old Thai woman presented with papulonecrotic tuberculid-like eruptions on her back and inframammary area with fever, nonproductive cough and weight loss. Chest radiograph showed diffuse bilateral reticulonodular opacities in both lungs with bilateral hilar lymph node enlargement. High resolution computed tomography (HRCT) of the lungs showed peribronchovascular interstitial thickening with multiple lymph nodes enlargement. Sputum for AFB was negative. Monotest (PPD) was negative. Skin biopsy revealed multiple naked granuloma compatible with sarcoidosis. She was treated with isoniazid, 300 mg/d, rifamipicin, 600 mg/d, ethambutal, 800, mg/d and pyrazinamide, 1000 mg/d for 2 months without improvement of skin and lung lesions. Prednisolone 45 mg/d was then administered adjunctive with isoniazid and rifampicin. After two weeks of treatment with prednisolone, the cutaneous and pulmonary lesions markedly improved Prednisolone was tapered in 6 months. Skin lesions, fever; dry cough disappeared and chest radiograph, HRCT of the chest were markedly improved.
OBJECTIVE: To investigate the shore-term therapeutic effects of AIDS complicated by tuberculosis. METHODS: Ninety-eight AIDS patients with tuberculosis living in a village in Henan province were observed. RESULTS: Among the 98 patients, fever, cough, night sweating, weight loss, and superficial lymph node swelling were the common symptoms. Highly active anti-retroviral therapy (HAART) combined with a 6-month anti-tuberculosis treatment protocol with streptomycin, isoniazid, rifampin, and pyrazinamide (2SHRZ/4HRZ) resulted in improvement of the patients' clinical symptoms and signs as well as the immune functions. CONCLUSION: AIDS complicated by tuberculosis should receive due medical attention and sputum smear examination for anti-acid bacillus combined with X-ray examination possesses good diagnostic value for tuberculosis in these patients, for whom short-term anti-tuberculosis treatment may have beneficial effects.
BACKGROUND: Abdominal tuberculosis is a rare location of this infection with a lot of diagnostic difficulties. The aim of this study was to review our experience of pediatric abdominal tuberculosis with that of the literature data. PATIENTS AND METHODS: A retrospective study was conducted over a 7-year period; 10 cases of abdominal tuberculosis in children were reviewed (6 girls and 4 boys, mean age: 11 years, extremes 4-14). Eight patients enrolled in this study satisfied the following criteria: a positive culture for mycobacterium tuberculosis on samples of ascites fluid, sputum, urine, abscess puncture and/or caseating granulomas on histologic examination of biopsies obtained by endoscopy, percutaneous aspiration or needle biopsy or exploratory laparotomy. Two other patients (patients No 1 & 5) had a favorable response within 10 weeks of antituberculous therapy. RESULTS: We observed 8 cases of peritoneal tuberculosis and 2 cases of intestinal tuberculosis. Extra-abdominal tuberculosis was found in 4 of those patients. Two patients had a contact with a tuberculosis positive individual. Nine children had BCG immunization. The main clinical features were abdominal distension (6 cases) and abdominal pain (6 cases). Abdominal ultrasonography visualized mesenteric lymphadenopathies (6 cases), an abdominal mass (5 cases), free (1 case) and localized ascites (1 case). Barium enema and small bowell series showed small bowel stenosis (1 case) and ileal ulcerations (1 case). Exploratory laparotomy, performed in 3 patients, showed whitish granulations and peritoneal abscesses with caseous necrosis on histology. Quadruple therapy with tuberculostatic agents was prescribed in all patients, associating isoniazid, rifampicin, pyrazinamide combined at the start of the treatment with streptomycin (7 cases) and ethambutol (3 cases). Short term outcome was favorable with no deaths. The long term outcome was complicated by persistent ascites (1 case) and the development of portal hypertension (1 case). CONCLUSION: Abdominal tuberculosis remains a rare localization with a lot of diagnostic difficulties.
Any tuberculosis of the child must be treated, whether it is a latent or a tuberculosis-disease. The treatment of pediatric tuberculosis is the same as the one for adults. The latter consists in a combination of several antimycobacterial drugs taken simultaneously per os in a single intake in the morning while fasting. The major problem is observance. Mediastinopulmonary tuberculosis: the treatment is six months long with in the first two months a combination of isoniazide (INH) 5 to 10 mg/kg per day, rifampicine (RMP) 10 to 20 mg/kg per day, and pyrazinamide (PZA) 20 to 30 mg/kg per day. The addition of ethambutol (EMB) 15 to 25 mg/kg per day is discussed. The four following months, the combination of INH and RMP is continued with the same dosage. The goal of treatment for tuberculosis-infection in the child is to prevent the appearance of tuberculosis-disease. INH in monotherapy for 12 months was first suggested. It allowed an 80% reduction of risk for ten years compared to a placebo group. In order to prevent the risks of failure related to a primary resistance to INH and to reduce the duration of treatment, a bitherapy (INH + RMP) has been proposed for six months. A recent study determines the efficiency of a three-month bitherapy.
Disseminated tuberculosis usually occurs in immunocompromised hosts. Involvement of bone marrow, liver, and spleen is infrequent. A previously healthy 15-year-old boy presented with body weight loss, prolonged fever, neck lymphadenopathy, pancytopenia, and hepatosplenic microabscesses within the recent month and was transferred to our hospital. Bone marrow studies showed hypocellular marrow. Based on his clinical manifestations, hemophagocytic syndrome was initially suspected. Pancytopenia resolved after administration of intravenous immunoglobulin but caseous necrosis and/or positive acid-fast stain were subsequently demonstrated in the lymph node biopsy and sputum. Cultures from these 2 specimens grew Mycobacterium tuberculosis. Fever continued in a low-grade pattern even under antituberculous therapy with rifampin, isoniazid, pyrazinamide and ethambutol. Five months after admission, fever subsided after splenectomy and liver wedge resection. Microscopic examinations of both the liver and spleen showed mycobacteria-related granulomatous inflammation and caseating necrosis. This report suggests that tuberculosis infection should be considered in the differential diagnosis in patients with prolonged fever, pancytopenia and hepatosplenic abscesses.
BACKGROUND: Hepatotoxicity is one of the most serious adverse effects of anti-tuberculosis drugs (ATD). Although many risk factors have been associated with ATD-induced hepatotoxicity, their influence on hepatitis severity has not been studied systematically. OBJECTIVES: To evaluate whether the presence of hepatotoxicity risk factors (advanced age, chronic liver disease, abuse of alcohol or other drugs or malnutrition) influences the severity of ATD-induced hepatotoxicity. DESIGN: A prospective cohort study of 471 active tuberculosis patients treated with isoniazid, rifampicin and pyrazinamide and followed in a tuberculosis clinic between January 1998 and July 2002. Incidence of hepatotoxicity and its severity according to the presence or absence of ATD-induced hepatitis risk factors was evaluated. RESULTS: The incidence of ATD-induced hepatotoxicity (serum transaminase > 3 x the upper limit of normal [ULN]) was 18.2% (42/231 patients) in the risk factor group and 5.8% (14/240 patients) in the non-risk factor group (OR 3.5; 95% CI 1.9-6.7; P < 0.001). Severe hepatotoxicity (transaminase > 10 x ULN) occurred in 6.9% (16/231) of the risk factor group and in 0.4% (1/240) (OR 17.7; 95% CI 2.3-135; P < 0.001) of the group without risk factors. CONCLUSIONS: ATD-induced hepatitis is significantly more frequent and more severe in patients with hepatotoxicity risk factors.
SETTING: In the first 2 years of the East Timor National TB Control Programme, 7960 new patients were treated (2RHZE/6HE) and 224 received a retreatment regimen (2SRHZE/1RHZE/4R3H3Z3E3). OBJECTIVE: To determine the nature and extent of drug-resistant tuberculosis (TB) in treatment failure cases in East Timor. METHODS: Sputum specimens from retreatment failure cases were processed and inoculated into a BACTEC MGIT960 tube and onto Löwenstein-Jensen media. Isolates were identified by Ziehl-Neelsen staining, hybridisation with nucleic acid probes and biochemical investigations. Susceptibility testing was performed using the radiometric proportion method. Pyrazinamide testing was performed using the Wayne indirect method. RESULTS: Eighteen patients failed retreatment (0.7% of new cases) and 14 were available for analysis. Mycobacterium tuberculosis was cultured from all specimens, despite considerable transport delays. Nine (64.3%) had multiple drug resistance (MDR-TB) and four (28.6%) had other drug resistance. All MDR-TB isolates were susceptible to amikacin, capreomycin and ethionamide, with most also susceptible to ciprofloxacin and para-aminosalicylic acid (PAS). CONCLUSIONS: An excellent TB control programme has been established in East Timor. If funds are available, East Timor provides an ideal setting for a small-scale DOTS-Plus programme to treat prevalent cases of MDR-TB, and this study could inform the second-line drug regimen.
SETTING: Four hundred and sixty-eight isoniazid (INH) resistant Mycobacterium tuberculosis isolates recovered from a selected Brazilian population. OBJECTIVE: To check for susceptibility to other chemotherapeutic drugs used in TB treatment, and to ascertain mutations involved in INH and rifampicin (RMP) resistance. DESIGN: Antimicrobial susceptibility to RMP, streptomycin and ethambutol (EMB) was evaluated by the resistance ratio method and pyrazinamide (PZA) by activity assay. Single strand conformation polymorphism (SSCP) and sequence analysis were performed in samples from this panel to confirm mutations in codon 315 of the katG and in a 69-bp region of the rpoB gene. RESULTS: Combined resistance to INH+RMP, INH+ PZA, INH+EMB, and INH+RMP+PZA was shown in respectively 272 (58.1%), 126 (26.9%), 47 (10%), 116 (24.8%) isolates. No katG mutation was found in 19 (39.6%) of 48 strains tested. Ser315Thr substitution was found in 29 (60.4%). All RMP-resistant strains tested (n = 25) showed rpoB mutations. S531L substitution was found in 15 (60%). CONCLUSION: INH-resistant strains isolated from selected Brazilian populations frequently show resistance to other first-line anti-tuberculosis drugs. rpoB mutation was responsible for RMP resistance in all strains. Among INHr strains, katG mutations were shown in only 60.4%. Genetic approaches targeting the rpoB gene but not the katG gene have a high sensitivity to detect resistance among Brazilian M. tuberculosis strains.
A 37-year-old man was diagnosed as being infected with human immunodeficiency virus (HIV), tuberculosis (TB), tuberculoma of the brain, and visceral leishmaniasis (VL) at the Rajendra Memorial Institute of Medical Sciences in Bihar, India. He had taken anti-tuberculosis therapy (ATT) for two and a half months and had episodes of convulsions with loss of consciousness, tongue bites, and incontinence of urine. The results of a neurologic examination were normal except for a left plantar extensor. He was positive for both HIV-I (confirmed by Western blot) and VL (confirmed by splenic aspirate). Treatment was initiated with amphotericin B lipid complex, a four-drug regimen (rifampicin, isoniazid, ethambutol, and pyrazinamide) of ATT, highly active antiretroviral therapy, anti-convulsants, and other supportive therapies. A repeat computed tomography scan of the brain showed the disappearance of the lesion followed by gliosis. After six months, he was also cured of VL. The triad of infections (HIV, VL, and TB) is a real threat in Bihar as an emerging combination of diseases of public health importance. Keeping these facts in mind, efforts to develop simple and cost effective diagnostic techniques coupled with affordable therapeutic facilities are urgently needed in developing countries.
BACKGROUND: Nations of the former Soviet Union have the world's highest reported levels of resistance to anti-tuberculosis drugs. We conducted the first national survey of anti-tuberculosis drug resistance in the Republic of Lithuania. METHODS: We tested Mycobacterium tuberculosis isolates from all incident culture-positive pulmonary TB patients registered in 2002. New patients were those treated for <1 month with any first-line anti-tuberculosis drug (isoniazid [INH], rifampin [RMP], ethambutol, or streptomycin); previously treated patients were those treated for > or =1 month. RESULTS: Of 1163 isolates, 475 (41%) were resistant to at least one first-line drug, and 263 (23%) were resistant to at least INH and RMP (MDR); this included 76/818 (9.3%) from new patients and 187/345 (54%) from previously treated patients. Of 52 MDR isolates randomly selected for extended testing at an international reference laboratory, 27 (51%, 95%CI 38-66) had resistance to pyrazinamide, 21 (40%, 95%CI 27-55) to kanamycin, and 9 (17%, 95%CI 8-30) to ofloxacin. CONCLUSIONS: The prevalence of MDR-TB in Lithuania is among the world's highest. Among MDR-TB isolates, aminoglycoside and fluoroquinolone resistance were common. To combat drug-resistant TB, Lithuania has implemented the WHO global TB control strategy (DOTS), and is developing an MDR-TB treatment program (DOTS-Plus).
The report describes an HIV/AIDS patient seen at a referral center in Mexico City, in whom a mycobacterial infection in the oral mucosa, probably tuberculosis (TB) was identified. The purpose is to describe the clinical and histological findings in an HIV-infected patient, who after being treated successfully for tuberculous lymphangitis 4 years ago, presented with a lingual ulcer as the only suggestive sign of recurrence of mycobacterial infection, probably M. tuberculosis. A 39-year-old man seen in the HIV clinic of the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" in Mexico City since 1991 for HIV infection. In 1999 the patient developed tuberculous lymphangitis; he was managed with a 4-drug regimen for 12 months, with improvement of local and systemic symptoms. In May of 2003, the patient presented a painful superficial lingual ulcer, 0.7 cm in diameter, well circumscribed, crateriform with slightly elevated, irregular and indurated borders, of 4 months duration. The histopathological examination showed chronic granulomatous inflammation with giant multinucleated cells, suggestive of mycobacterial infection, and recurrence of TB was considered. Rifampin, isoniazide, pyrazinamide, ethambutol and streptomycin were administered. The lingual lesion improved with partial healing at the first week and total remission at 45 days after the beginning of the antituberculous treatment. In June, 2003, the patient began highly active antiretroviral therapy (HAART) that included two NRTIs and one NNRTI. At 7 months of follow-up, the patient remains free of lingual lesions. The particularity of the present case is that the lingual ulcer was the only sign of infection by mycobacteria, suggestive of TB, in an HIV/AIDS patient that probably represented a recurrence of a previous episode.
This report describes the first successful isolation and identification of mycobacterial infection in humans and animals of Chad. All mycobacterial strains from human specimens were M. tuberculosis and strains from animal specimens (cattle) were M. bovis. None of the 10 of M. tuberculosis strains tested for antibiotic resistance were multidrug resistant. Due to the intrinsic resistance of M. bovis to pyrazinamide and the growing number of tuberculosis cases in HIV-infected people in Africa and elsewhere, more information on the potential of M. bovis for human infection is needed to guide disease control policy.
From June 1668 to June 2002, we have studied at the Pneumology Clinic of Fann Hospital, pulmonary tuberculosis among 9 pregnant women. The average age was 26 years old and the consultation's delay was 5 months. All our patients had a productive cough and an evening fever coupled with a thoracic pain and a deterioration of the general condition in 7 patients (77.7%). The dyspnea and the heamoptisis were a consultation motive for 44.4% and 33.3% of the patients. The evolution of pregnancies was 29 weeks. They had all benefited from the intradermal reaction with tuberculin (IDRT) with an average diameter of 11.7 mm; it was negative in one patient. The bacilloscopy systematically done was negative in 2 patients. At the front thoracic radiography, we have found basal lesions unilateral in more than half of the cases and excavated in 44.4% of cases. They benefited from an antitubercular treatment (Rifampicine (R) + Isoniazide (H) + Pyrazinamide (Z) with a good clinical, biological, bacteriological and radiological progression. From the obstetrical point of view, there was an abortion after 5 months, 2 premature deliveries between the 7th and the 8th month and 6 normal deliveries at 9 months. Babies born from bacillary mothers systematically received an antitubercular treatment with breast feeding. In conclusion, pregnant women with pulmonary tuberculosis essentially pose a therapeutic problem, requiring a good collaboration between the lung specialist, the gyneco-obstetrician and the pediatrician. It could be more hazardous not to act early in treating a pregnant women with pulmonary tuberculosis.
This case report try to point out the importance of early diagnosis, and an appropriate treatment in multifocal tuberculosis including a testicular localization. A 25 year-old male with a past history of tuberculosis contact and untreated chronic cough with haemoptysis is admitted in our in-patient clinic. Eighteen months earlier, he presented a long course fever, with lumbar pain. Thereafter, the patient condition worsened as he lost weight and developed an enlargement of the right testicle with an scrotal abscess fistulous and a meningo-encephalitis clinical presentation. The bacilloscopy performed on gastric specimen and scrotal caseous was negative. The cerebrospinal fluid was clear and showed a mixed formula with 370 cells including 50% of lymphocytes, an elevated albumin (0.70g/l) and low glucose (0.10g/l) . Sterile pus was detected in urine. The tuberculosis skin test was positive. In addition to the clinical and epidemiological context, the radiological findings (chest and spine X-ray, testicular ultrasonography, cerebral CT Scan) were consistent with multifocal tuberculosis infection with lung miliary, epididymal-orchitis, and brain tuberculomas. The patient was treated successfully using a two-step protocol: two-month treatment with isoniazid, rifampicin, ethambutol and pyrazinamid altogether; followed by a seven-month regimen with isoniazid and rifampicin. Nevertheless,the patient is likely to develop static trouble and infertility because of the spine sequela and testicle atrophy he presented.
Antituberculosis medications are extremely well tolerated by children and have proved to be very successful. The newer regimens of intensive short-course chemotherapy for tuberculosis have several advantages over traditional two-drug regimens, including faster sterilization and bactericidal action, shorter duration over which patient noncompliance can occur, less expenditure of resources for monitoring treatment, lower failure and relapse rates, and broader coverage for possible drug-resistant M. tuberculosis. The currently recommended regimen for pulmonary and most extrapulmonary forms of tuberculosis in children is 6 months of isoniazid and rifampin supplemented during the first 2 months by pyrazinamide. Treatment during the first 1 to 2 months should, if possible, be daily but the last 4 to 5 months of therapy can be either daily or twice weekly under direct observation of a health-care professional. For patients in whom social or other constraints prevent reliable self-administration of daily treatment in the initial phase, medications may be given twice weekly from the beginning under close observation. For these situations, a total duration of treatment of 6 to 9 months is reasonable. Non-life-threatening forms of extrapulmonary tuberculosis can be treated in the same manner as pulmonary tuberculosis. Although tuberculous meningitis probably will respond to these regimens, the relative lack of data at present leads most experts to recommend total durations of between 6 and 12 months for this form of tuberculosis. The major limitation to controlling tuberculosis in the United States is noncompliance or nonadherence to medications by patients. The physician and other health-care providers must devote a great deal of their time and energy to ensuring adherence with medications and take whatever steps are necessary to make sure that the child with tuberculosis is adequately treated.
SETTING: A local tuberculosis control program. OBJECTIVE: To examine treatment completion rates of patients with Mycobacterium bovis disease and compare them with those of patients with M. tuberculosis disease. DESIGN: Retrospective review of data from a tuberculosis surveillance computer database. RESULTS: Data from 167 M. bovis patients and 928 M. tuberculosis patients were examined. Rates of treatment completion were not significantly different (78% vs. 82%, chi2 = 1.60, P = 0.174), although death was more frequent among M. bovis patients (15% vs. 7%). The median time to treatment completion was 94 days longer for M. bovis patients. CONCLUSION: Overall, treatment completion rates of M. bovis and M. tuberculosis patients were comparable, although the death rate was higher for M. bovis patients. The latter finding may be related to a particularly high death rate among HIV-infected M. bovis patients. Therapy duration was longer for M. bovis patients, probably because resistance to pyrazinamide prevented the use of a short-course (6-month) regimen.